Total glucosides of Danggui Buxue Tang attenuates bleomycin-induced pulmonary fibrosis via inhibition of extracellular matrix remodelling.

OBJECTIVES: This study was designed to investigate the antifibrosis effects and possible mechanism of action of total glucosides of Danggui Buxue Tang (DBTG) on bleomycin-induced pulmonary fibrosis in rats.

METHODS: DBTG was extracted from Radix Astragali and Radix Angelicae Sinensis. Pulmonary fibrosis was induced by intratracheal instillation of bleomycin (5 mg/kg) in Wistar rats. Subsequently, the rats received daily intragastric administration of DBTG (16, 32 or 64 mg/kg per day) or cortisone (3 mg/kg) 1 day after bleomycin instillation for 4 weeks. Histological changes in the lung were evaluated by hematoxylin and eosin and Masson's trichrome staining. Markers of fibrosis in serum were determined by radioimmunoassay. The mRNA expression of metalloproteinases 1 and 9 (MMP-1, MMP-9) and tissue inhibitor of metalloproteinase 1 (TIMP-1) in lung tissue were detected by reverse transcription PCR.

KEY FINDINGS: DBTG administration attenuated the degree of alveolitis and lung fibrosis, and markedly reduced the elevated levels of hyaluronic acid, laminin, type III procollagen and type IV collagen in serum. DBTG decreased the mRNA levels of MMP-9 and TIMP-1. MMP-1 expression was only moderately decreased by DBTG.

CONCLUSIONS: DBTG had an inhibitory effect on bleomycin-induced pulmonary fibrosis and its effect may be associated with the ability of DBTG to inhibit the synthesis of extracellular matrix and balance the MMP/TIMP-1 system.